TY - JOUR A1 - Gossmann, Matthias A1 - Thomas, Ulrich A1 - Horváth, András A1 - Dragicevic, Elena A1 - Stoelzle-Feix, Sonja A1 - Jung, Alexander A1 - Raman, Aravind Hariharan A1 - Staat, Manfred A1 - Linder, Peter T1 - A higher-throughput approach to investigate cardiac contractility in vitro under physiological mechanical conditions JF - Journal of Pharmacological and Toxicological Methods Y1 - 2020 U6 - https://doi.org/10.1016/j.vascn.2020.106843 VL - 105 IS - Article 106843 PB - Elsevier CY - New York, NY ER - TY - JOUR A1 - Brockhaus, Moritz K. A1 - Behbahani, Mehdi A1 - Muris, Farina A1 - Jansen, Sebastian V. A1 - Schmitz- Rode, Thomas A1 - Steinseifer, Ulrich A1 - Clauser, Johanna C. T1 - In vitro thrombogenicity testing of pulsatile mechanical circulatory support systems: Design and proof-of-concept JF - Artificial Organs N2 - Thrombogenic complications are a main issue in mechanical circulatory support (MCS). There is no validated in vitro method available to quantitatively assess the thrombogenic performance of pulsatile MCS devices under realistic hemodynamic conditions. The aim of this study is to propose a method to evaluate the thrombogenic potential of new designs without the use of complex in-vivo trials. This study presents a novel in vitro method for reproducible thrombogenicity testing of pulsatile MCS systems using low molecular weight heparinized porcine blood. Blood parameters are continuously measured with full blood thromboelastometry (ROTEM; EXTEM, FIBTEM and a custom-made analysis HEPNATEM). Thrombus formation is optically observed after four hours of testing. The results of three experiments are presented each with two parallel loops. The area of thrombus formation inside the MCS device was reproducible. The implantation of a filter inside the loop catches embolizing thrombi without a measurable increase of platelet activation, allowing conclusions of the place of origin of thrombi inside the device. EXTEM and FIBTEM parameters such as clotting velocity (α) and maximum clot firmness (MCF) show a total decrease by around 6% with a characteristic kink after 180 minutes. HEPNATEM α and MCF rise within the first 180 minutes indicate a continuously increasing activation level of coagulation. After 180 minutes, the consumption of clotting factors prevails, resulting in a decrease of α and MCF. With the designed mock loop and the presented protocol we are able to identify thrombogenic hot spots inside a pulsatile pump and characterize their thrombogenic potential. Y1 - 2021 U6 - https://doi.org/10.1111/aor.14046 SN - 1525-1594 VL - 45 IS - 12 SP - 1513 EP - 1521 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Knox, Ronald A1 - Bruggemann, Andrea A1 - Gossmann, Matthias A1 - Thomas, Ulrich A1 - Horváth, András A1 - Dragicevic, Elena A1 - Stoelzle-Feix, Sonja A1 - Fertig, Niels A1 - Jung, Alexander A1 - Raman, Aravind Hariharan A1 - Staat, Manfred A1 - Linder, Peter T1 - Combining physiological relevance and throughput for in vitro cardiac contractility measurement JF - Biophysical Journal N2 - Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models result from an improper mechanical environment. We cultured hiPSC-CMs in a 96-well format on hyperelastic silicone membranes imitating their native mechanical environment, resulting in physiological responses to compound stimuli.We validated cell responses on the FLEXcyte 96, with a set of reference compounds covering a broad range of cellular targets, including ion channel modulators, adrenergic receptor modulators and kinase inhibitors. Acute (10 - 30 min) and chronic (up to 7 days) effects were investigated. Furthermore, the measurements were complemented with electromechanical models based on electrophysiological recordings of the used cell types.hiPSC-CMs were cultured on freely-swinging, ultra-thin and hyperelastic silicone membranes. The weight of the cell culture medium deflects the membranes downwards. Rhythmic contraction of the hiPSC-CMs resulted in dynamic deflection changes which were quantified by capacitive distance sensing. The cells were cultured for 7 days prior to compound addition. Acute measurements were conducted 10-30 minutes after compound addition in standard culture medium. For chronic treatment, compound-containing medium was replaced daily for up to 7 days. Electrophysiological properties of the employed cell types were recorded by automated patch-clamp (Patchliner) and the results were integrated into the electromechanical model of the system.Calcium channel agonist S Bay K8644 and beta-adrenergic stimulator isoproterenol induced significant positive inotropic responses without additional external stimulation. Kinase inhibitors displayed cardiotoxic effects on a functional level at low concentrations. The system-integrated analysis detected alterations in beating shape as well as frequency and arrhythmic events and we provide a quantitative measure of these. Y1 - 2020 U6 - https://doi.org/10.1016/j.bpj.2019.11.3104 SN - 0006-3495 N1 - Raman, Arayind Hariharan im Artikel unter dem Namen: Raman, Alexander H. VL - 118 IS - Issue 3, Supplement 1 SP - 570a PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Schopp, Christoph A1 - Doll, Timo A1 - Gräser, Ulrich A1 - Harzheim, Thomas A1 - Heuermann, Holger A1 - Kling, Rainer A1 - Marso, Michael T1 - Capacitively Coupled High-Pressure Lamp Using Coaxial Line Networks JF - IEEE Transactions on Microwave Theory and Techniques N2 - This paper describes the development of a capacitively coupled high-pressure lamp with input power between 20 and 43 W at 2.45 GHz, using a coaxial line network. Compared with other electrodeless lamp systems, no cavity has to be used and a reduction in the input power is achieved. Therefore, this lamp is an alternative to the halogen incandescent lamp for domestic lighting. To serve the demands of domestic lighting, the filling of the lamp is optimized over all other resulting requirements, such as high efficacy at low induced powers and fast startups. A workflow to develop RF-driven plasma applications is presented, which makes use of the hot S-parameter technique. Descriptions of the fitting process inside a circuit and FEM simulator are given. Results of the combined ignition and operation network from simulations and measurements are compared. An initial prototype is built and measurements of the lamp's lighting properties are presented along with an investigation of the efficacy optimizations using large signal amplitude modulation. With this lamp, an efficacy of 135 lmW -1 is achieved. Y1 - 2016 U6 - https://doi.org/10.1109/TMTT.2016.2600326 SN - 0018-9480 VL - 64 IS - 10 SP - 3363 EP - 3368 PB - IEEE CY - New York, NY ER - TY - RPRT A1 - Stölzle-Feix, Sonja A1 - Thomas, Ulrich A1 - Engelstädter, Max A1 - Goßmann, Matthias A1 - Linder, Peter A1 - Staat, Manfred A1 - Raman, Aravind Hariharan A1 - Jung, Alexander A1 - Fertig, Niels T1 - Plattformtechnologie für kardiale Sicherheitspharmakologie basierend auf teilsynthetischem Herzmuskelgewebe (FLEXcyte) : gemeinsamer FuE-Abschlussbericht aller Partner des Verbundprojektes : Projektlaufzeit: 01.10.2018 bis 30.09.2020 Y1 - 2021 U6 - https://doi.org/10.2314/KXP:1813208581 N1 - Förderkennzeichen BMBF 02P18K020-021 Verbundnummer 01185221 PB - Nanion Technologies GmbH CY - München ER -